Organ failure syndromes that cause substantial morbidity and death often complicate critical illness due to severe infection or traumatic injury. Recent advances in computational biology and high-throughput technologies (e.g. microarrays, highly parallel single nucleotide polymorphism (SNP) analysis, and proteomics) have generated considerable interest in developing a more global understanding of complex biological systems. The application of these technologies to critical illness offers the potential to define maladaptive programs of gene expression induced by infection, trauma or other inflammatory triggers and to detect biomarkers and genetic polymorphisms that are associated with these responses. These tools also provide a means to discover novel gene function and to identify potential therapeutic targets. Investigators that plan to use genomic and proteomic approaches to study critical illness and injury are presented with major challenges regarding the unique demands that these methods place on resources, experimental design, and analysis. Furthermore, investigations in this setting face unique requirements related to patient safety, vulnerability, and privacy as well as other ethical considerations specific to performing genomic research. The Functional Genomics of Critical Illness and Injury Symposium has been held annually for the past two years to address these needs (www.cc.nih.gov/ccmd/Symposium/). This application seeks funding for the Physiological Genomics of Critical Illness and Injury Symposium (April 21-22, 2005), the goal of which is to bring together those with the diverse skills sets necessary to apply genomics and systems analysis to the study of critical illness and injury. The objectives are three-fold: education, consensus, and collaboration. Importantly, there is no other venue by which this group of investigators might meet to discuss the application of genomic technology, ethics, and human values to the study of critical illness and injury.